Abstract:
Mouth dissolving tablets (MDT) are useful in patients, such as pediatric, geriatric, bedridden, or developmentally disabled, who may face difficulty in swallowing conventional tablets or capsules and liquid orals or syrup, leading to ineffective therapy, with persistent nausea, sudden episodes of allergic attack, or coughing for those who have an active life style. Over the past three decades, mouth dissolving tablets have gained considerable attention as a preferred alternative to conventional tablets and capsules due to better patient compliance The objective of this article is to review the development of MDTs, challenges in formulation, benefit, limitation ,new MDT technologies and evaluation methodologies.

REFERENCE ID: PHARMATUTOR-ART-1706

INTRODUCTION
1. Mouth Dissolving Tablet
Oral drug delivery has been known for decades as the most widely utilized route of administration among all the routes that have been explored for the systemic delivery of drugs via various pharmaceutical products of different dosage forms. The reason that the oral route achieved such popularity may be in part attributed to its ease of administration.
All the pharmaceutical products formulated for systemic delivery via the oral route of administration, irrespective of the mode of delivery (immediate, sustained or controlled release) and the design of dosage forms (solid, dispersion or liquid) must be developed within the intrinsic characteristics of GI physiology. Therefore, a fundamental understanding of various disciplines, including GI physiology, pharmacokinetics, pharmacodynamics and formulation design are essential to achieve a systemic approach to the successful development of pharmaceutical dosages forms. The more sophisticated a delivery system, the greater is the complexity of these various disciplines involved in the design and optimization of the delivery system. In any case, the scientific framework required for the successful development of an oral drug delivery system consists of a basic understanding of the following three aspects.

* Physicochemical, pharmacokinetic and pharmacodynamics characteristics of the drug.
* The anatomic and physiologic characteristics of the GIT.
* Physicochemical characteristics and the drug delivery mode of the dosage form to be designed1.

Oral routes of drug administration have wide acceptance up to 50-60% of total dosage forms. The most popular solid dosage forms are being tablets and capsules; one important drawback of this dosage forms for some patients, is the difficulty to swallow.

Drinking water plays an important role in the swallowing of oral dosage forms. Often times people experience inconvenience in swallowing conventional dosage forms such as tablet when water is not available, in the case of the motion sickness (kinetosis) and sudden episodes of coughing during the common cold, allergic condition and bronchitis. For these reasons, tablets that can rapidly dissolve or disintegrate in the oral cavity have attracted a great deal of attention. Rapidly dissolving or disintegrating tablets are not only indicated for people who have swallowing difficulties, but also are ideal for active people2.

Mouth dissolving tablets are also called as fast dissolving tablets, melt-in mouth tablets, Orodispersible tablets, rapimelts, porous tablets, quick dissolving etc. Mouth dissolving tablets are those when put on tongue, disintegrate instantaneously releasing the drug which dissolves or disperses in the saliva .Faster the drug into solution, quicker the absorption and onset of clinical effect.

Fig no.1: Conceptual Diagram of MDT’s

Some drugs are absorbed from the mouth, pharynx and esophagus as the saliva passes down into the stomach. In such cases, bioavailability of drug is significantly greater than those observed from conventional tablets dosage form. The bioavailability of some drugs may be increased due to absorption of drug in oral cavity and also due to pregastric absorption of saliva containing dispersed drugs that pass down into the stomach. Moreover, the amount of drug that is subjected to first pass metabolism is reduced as compared to standard tablet. The advantage of mouth dissolving dosage forms are increasingly being recognized in both, industry and academics3.

Mouth dissolving drug delivery systems (MDDDS) are a new generation of formulations which combine the advantages of both liquid and conventional tablet formulations and at the same time, offer added advantages over both traditional dosage forms. They provide the convenience of a tablet formulation and also allow the ease of swallowing provided by a liquid formulation. MDDDS offer the luxury of much more accurate dosing than the primary alternative, oral liquids. This segment of formulation is especially designed for dysphagic, geriatric, pediatric, bed-ridden, travelling and psychotic patients who are unable to swallow or refuse to swallow conventional oral formulations. They do not require water for administration, thus are good alternative for travelers and for bed ridden patients. They simply vanish when placed in the mouth, so cannot be hidden in mouth by psychotic patients. These products not only increase the patient’s compliance but also fetch large revenues to manufacturers due to line extension of the existing formulation. In the recent past, several new advanced technologies have been introduced for the formulation of mouth dissolving tablets (MDTs) with very interesting features, like extremely low disintegration time, exceptional taste masking ability, pleasant mouth feel and sugar free tablets for diabetic patients. The technologies utilized for fabrication of MDDDS include lyophilization, moulding, direct compression, cotton candy process, spray drying, sublimation, mass extrusion, nanonization and quick dissolve film formation. These techniques are based on the principles of increasing porosity and/or addition of superdisintegrants and water soluble excipients in the tablets. The formulations prepared from these techniques differ from each other on the basis of the factors like mechanical strength of final product, drug and dosage form stability, mouth feel, taste, rate of dissolution of the formulation in saliva, rate of absorption from saliva and overall drug bioavailability5.

Although, numerous technologies had been developed for the fabrication of these unique dosage forms in last two decades, but so far, no standardized technique has been designed or mentioned in pharmacopoeias for their evaluation except in European Pharmacopoeia (EP), which defines Orodispersible tablets as “uncoated tablets intended to be placed in the mouth where they disperse rapidly before being swallowed”. EP also specifies that the Orodispersible tablets should disintegrate within 3 minutes when subjected to conventional disintegration test used for tablets and capsules. Orally Disintegrating (OD) tablet technology has been approved by United state Pharmacopoeia (USP), Center for Drug Evaluation and Research (CDER). USFDA defined OD tablet as ” A solid dosage form containing medicinal substance , which disintegrate rapidly ,usually within a matter of seconds , when placed upon the tongue”6.

Despite various terminologies used, Mouth dissolving tablets are here to offer unique form of dug delivery with advantages over the conventional oral solid dosage forms.

1.1. Criteria for Mouthdissolving Drug Delivery System7
The tablets should
* Not require water to swallow, but it should dissolve or disintegrate in the mouth in matter of seconds.
* Be compatible with taste masking.
* Be portable without fragility concern.
* Have a pleasant mouth feel.
* Leave minimum or no residue in the mouth after oral administration.
* Exhibit low sensitive to environmental condition like temperature and humidity
* Allow the manufacture of the tablet using conventional processing and packaging equipments, at low cost.

1.2. Salient Feature of MouthDissolving Drug Delivery System 7
* Ease of Administration to the patient who cannot swallow, such as the elderly, stroke victims, bedridden patients and patient who refuse to swallow such as pediatric, geriatric & psychiatric patients.
* No need of water to swallow the dosage form, which is highly convenient feature for patients who are traveling and do not have immediate access to water.
* Rapid dissolution and absorption of the drug, which will produce quick onset of action.
* Some drugs are absorbed from the mouth, pharynx and esophagus as the saliva passes down into the stomach. In such cases bioavailability of drug is increased.
* Pregastric absorption can result in improved bioavailability and as a result of reduced dosage; improve clinical performance through a reduction of unwanted effects.
* Good mouth feel property helps to change the perception of medication as bitter pill particularly in pediatric patient.
* The risk of chocking or suffocation during oral administration of conventional formulation due to physical obstruction is avoided, thus providing improved safety.
* New business opportunity like product differentiation, product promotion, patent extensions and life cycle management.

1.3 Benifits of MouthDissolving Tablets 7:
* Administered without water, anywhere, any time.
* Suitability for geriatric and pediatric patients, who experience difficulties in swallowing and for the other groups that may experience problems using conventional oral dosage form, due to being mentally ill, the developmentally disableand the patients who are un-cooperative, or are on reduced liquid intake plans or are nauseated.
* Beneficial in cases such as motion sickness, sudden episodes of allergic attack orcoughing, where an ultra-rapid onset of action required.
* An increased bioavailability, particularly in cases of insoluble and hydrophobic drugs, due to rapid disintegration and dissolution of these tablets.
* Stability for longer duration of time, since the drug remains in solid dosage form till it is consumed. So, it combines advantage of solid dosage form in terms of stability and liquid dosage form in terms of bioavailability.
* Pregastric absorption can result in improved bioavailability, reduced dose and improved clinical performance by reducing side effects.

1.5.1. Palatability
As most drugs are unpalatable, orally disintegrating drug delivery systems usually contain the medicament in a taste-masked form. Delivery systems disintegrate or dissolve in patient’s oral cavity, thus releasing the active ingredients which come in contact with the taste buds; hence, taste-masking of the drugs becomes critical for patient compliance.

1.5.2. Mechanical strength
In order to allow ODTs to disintegrate in the oral cavity, they are made of either very porous and soft-molded matrices or compressed into tablets with very low compression force, which makes the tablets friable and/or brittle, difficult to handle and often requiring specialized peel-off blister packing that may add to the cost.

1.5.3. Hygroscopicity
Several orally disintegrating dosage forms are hygroscopic and cannot maintain physical integrity under normal conditions of temperature and humidity. Hence, they need protection from humidity which calls for specialized product packaging.

1.5.4. Amount of drug
The application of technologies used for ODTs is limited by the amount of drug that can be incorporated into each unit dose. For lyophilized dosage forms, the drug dose must be lower than 400 mg for insoluble drugs and less than 60 mg for soluble drugs. This parameter is particularly challenging when formulating a fast- dissolving oral films or wafers.

1.5.5. Aqueous solubility
Water soluble drugs pose various formulation challenges because they form eutectic mixtures, which result in freezing-point depression and the formation of a glassy solid that may collapse upon drying because of loss of supporting structureduring the sublimation process. Such collapse sometimes can be prevented by using various matrix-forming excipients such as mannitol than can induce crystallinity and hence, impart rigidity to the amorphous composite.

1.5.6. Size of tablet
The degree of ease when taking a tablet depends on its size. It has been reported that the easiest size of tablet to swallow is 7-8 mm while the easiest size to handle was one larger than 8 mm. Therefore, the tablet size that is both easy to take and easy to handle is difficult to achieve.